Supplementary Table S1: List of validated hits from N minus RAS screen S.N. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Gene Methyl CpG Binding Protein 2 (MECP2) Orthodenticle Homeobox 2 (OTX2) Target Of Myb1 (Chicken) (TOM1) G Protein-Coupled Receptor 171 (GPR171) Flotillin 2 (FLOT2) Chromosome 12 Open Reading Frame 74 (C12ORF74) Histone Cluster 1, H2bn (HIST1H2BN) Histone Cluster 1, H3f (HIST1H3F) Solute Carrier Family 25, Member 41 (SLC25A41) Chimerin 1 (CHN1) Zinc Finger Protein 658 (ZNF658) Lipoxygenase Homology Domains 1 (LOXHD1) Regulator Of G-Protein Signaling 3 (RGS3) Chloride Channel, Voltage-Sensitive Kb (CLCNKB) Calmodulin 3 (Phosphorylase Kinase, Delta) (CALM3) Entrez Gene ID 4204 5015 10043 29909 2319 338809 8341 8968 284427 1123 26149 125336 5998 1188 808 Supplementary Table S2: Amplicons in Human Cancer (from Broad Institute TCGA Copy Number Portal) Peak Region chr7:55065906-55102668 chr8:128739771-128769210 chr11:69460105-69484581 chr17:37855834-37875909 chr19:30306820-30315735 chr12:69212831-69260428 chr3:169416569-169490229 chr12:58135796-58155222 chr11:70140426-70213455 chr1:150519259-150703005 chr3:181256573-181731927 chr11:77613200-77640847 chr8:38171486-38254058 chr5:1288615-1299329 chr4:55008314-55104469 chr12:25344325-25370603 chr8:41761807-41929152 chr15:99056932-99774542 chr1:204353015-204538342 chr12:889902-1041097 chr20:30203029-30315025 chr1:40377907-40416849 chr1:242980673-247812431 chr19:39770395-39892270 chr17:57922442-57943519 chrX:153016891-153342426 (MECP2 containing amplicon) chr7:92173409-92556768 chr1:160989893-161115583 chr8:101324125-101642253 chr20:52156927-52364760 chr8:37492872-37529770 chr6:43638636-43987936 chr3:197077908-197335218 chr13:113757997-114302622 #Genes in Peak 1 1 2 1 1 2 2 6 1 8 3 1 2 1 1 3 1 6 3 12 2 0 84 9 1 18 Residual Qvalue 0 1.74E-272 2.12E-222 1.22E-204 5.49E-183 1.07E-144 2.03E-124 3.76E-122 5.18E-118 3.65E-113 9.82E-81 1.45E-78 2.04E-71 1.40E-60 1.46E-51 2.82E-44 4.94E-41 2.14E-37 1.58E-36 9.28E-34 9.01E-33 7.80E-29 1.22E-28 1.27E-28 1.34E-27 1.21E-26 Overall 0.382 0.453 0.208 0.199 0.24 0.211 0.335 0.205 0.204 0.37 0.328 0.169 0.234 0.317 0.114 0.245 0.259 0.145 0.363 0.247 0.391 0.145 0.352 0.217 0.242 0.176 Focal 0.068 0.129 0.106 0.054 0.066 0.053 0.118 0.045 0.102 0.1 0.118 0.068 0.067 0.071 0.05 0.041 0.06 0.064 0.046 0.058 0.045 0.051 0.072 0.043 0.048 0.059 Highlevel 0.084 0.139 0.065 0.038 0.055 0.04 0.093 0.033 0.062 0.078 0.089 0.031 0.057 0.076 0.023 0.047 0.055 0.018 0.066 0.043 0.073 0.018 0.06 0.035 0.029 0.018 4 9 4 2 0 5 1 13 8.22E-26 2.07E-25 9.37E-25 3.87E-24 1.51E-23 1.62E-21 2.59E-21 1.20E-19 0.363 0.369 0.417 0.401 0.223 0.197 0.315 0.179 0.039 0.077 0.061 0.043 0.059 0.043 0.112 0.058 0.05 0.069 0.104 0.083 0.051 0.027 0.078 0.03 chr11:102266643-102488711 chr17:27148617-27422161 chr20:62187416-62219648 chr19:15338573-15408584 chr14:36544027-37264674 chr6:20396454-20522290 chr8:144939389-145147978 chr9:35654478-35737197 chr11:66980818-67054144 chr4:1778801-1816690 chr18:20358314-20503269 chr17:73466243-73637996 chr6:107198296-107289865 chr11:34639284-34838823 chr10:76501637-77227430 chr2:178085599-178160931 chr8:80714469-81835247 chr17:77765982-77821663 chr5:37909815-44676519 chr4:73903374-74158212 chr14:105197567-105318962 chr22:18613737-22139416 chr19:55547934-58878226 chr8:55091227-55382067 chr6:64084316-64402884 chr12:66217394-66241372 chr5:176445948-176904216 chr9:4894234-5591850 chr19:35494834-36225620 chr14:20501368-21697941 chr19:10238547-10877387 chr7:146690968-158383607 chr17:48773492-49002559 chr10:5507029-5769453 chr13:73907772-73972011 chr7:708774-1243749 chr6:11203906-11588708 chr2:60243955-63176269 chr3:13669693-13758663 3 14 39 2 9 1 12 10 3 2 1 8 2 1 10 4 5 3 52 2 7 90 147 1 2 2 15 8 37 66 28 112 7 4 0 22 2 21 2 1.99E-19 1.97E-18 1.61E-17 1.95E-17 2.45E-15 1.01E-14 1.55E-14 1.99E-13 2.88E-13 2.44E-12 1.35E-11 6.82E-11 1.13E-09 1.69E-09 2.01E-09 1.47E-08 3.48E-08 5.70E-07 5.95E-07 1.78E-06 2.49E-06 3.08E-06 5.70E-06 8.28E-06 1.45E-05 1.58E-05 1.60E-05 2.00E-05 4.83E-05 7.10E-05 2.28E-04 5.87E-04 9.47E-04 0.003 0.00339 0.00349 0.00387 0.0124 0.0347 0.134 0.185 0.397 0.194 0.144 0.205 0.424 0.138 0.176 0.107 0.143 0.258 0.105 0.127 0.107 0.163 0.385 0.256 0.288 0.095 0.14 0.14 0.192 0.349 0.153 0.197 0.166 0.126 0.229 0.144 0.176 0.339 0.218 0.167 0.156 0.375 0.203 0.193 0.115 0.035 0.048 0.056 0.04 0.043 0.037 0.105 0.044 0.072 0.042 0.036 0.07 0.024 0.033 0.035 0.043 0.041 0.072 0.038 0.039 0.045 0.038 0.045 0.045 0.038 0.037 0.052 0.03 0.047 0.049 0.034 0.045 0.031 0.037 0.031 0.046 0.043 0.031 0.033 0.019 0.018 0.079 0.028 0.019 0.029 0.108 0.019 0.022 0.016 0.022 0.027 0.015 0.014 0.013 0.013 0.082 0.024 0.061 0.014 0.013 0.014 0.017 0.067 0.015 0.026 0.015 0.019 0.035 0.014 0.021 0.04 0.02 0.022 0.029 0.045 0.026 0.014 0.01 chr8:115442722-118152629 9 0.0752 0.43 chr9:139822542-140366608 44 0.0981 0.143 chr2:113962850-114139862 2 0.102 0.16 chr10:123172835-123398895 1 0.117 0.096 chr13:27260341-28888798 23 0.146 0.135 chr7:116314195-116508848 2 0.156 0.346 Note: Q values (False Discovery Values) below 0.25 are considered significant 0.083 0.043 0.034 0.029 0.031 0.027 0.109 0.011 0.011 0.009 0.023 0.041 Supplementary Table S3: Cancer cell lines used in current study with their MECP2 expression and RAS/MAPK/PI3K pathways mutation status (based on COSMIC, canSAR, ATCC, and CCLE databases) Cell lines BREAST MECP2 overexpressing cell lines: BT549 MDAMB468 MDAMB453 BT20 MCF7 Cell lines with low MECP2: ZR75-1 MDAMB231 T47D HCC38 LUNG MECP2 overexpressing cell lines: NCI-H1755 NCI-H23 NCI-H1993 NCI-H2228 NCI-H2170 NCI-H2009 NCI-H522 NCI-H1563 Cell lines with low MECP2: NCI-H1437 NCI-H1395 NCI-H838 NCI-H2347 OVARIAN MECP2 overexpressing cell lines: EFO21 IGROV1 SKOV3 RAS mutation Other relevant mutations (in MAPK and PI3K pathways) Wild-type Wild-type Wild-type Wild-type Wild-type PTENV275X PTENA72fsX5 PTENE307K; PIK3CAH1047R PIK3CAP539R; PIK3CAH1047R PIK3CAE545K Wild-type KRASG13D Wild-type Wild-type PTENL108R BRAFG464V; NF2E231* PIK3CAH1047R Wild-type KRASG12C Wild-type Wild-type Wild-type KRASG12A Wild-type Wild-type BRAFG468A Wild-type Wild-type Wild-type NRASQ61R Wild-type Wild-type Wild-type MET amplification EML4-ALK fusion BRAFG469A PTENY155C; PIK3CAR38C; AKT2V198A ERBB2 amplification; PIK3CAH1047R CAOV3 OVCAR4 Cell lines with low MECP2: OVCAR3 OVCAR5 OVCAR8 Wild-type Wild-type PTENW274G Wild-type KRASG12V KRASP121H CCNE1 amplification; AKT2 amplification ERBB2G776V
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